A Phase II Randomized Trial Comparing Standard and Low Dose Rituximab: Initial Treatment of Progressive Chronic Lymphocytic Leukemia in Elderly Patients Using Alemtuzumab and Rituximab
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 31
- 试验地点
- 204
- 主要终点
- Proportion of Patients With Complete Response (CR)
研究概览
简要总结
RATIONALE: Monoclonal antibodies, such as rituximab and alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer killing substances to them. Giving rituximab together with alemtuzumab may kill more cancer cells.
PURPOSE: This randomized phase II trial is studying two different doses of rituximab to compare how well they work when given together with alemtuzumab in treating older patients with progressive chronic lymphocytic leukemia.
详细描述
OBJECTIVES:
Primary
- To compare the rate of complete and overall response in elderly patients with progressive chronic lymphocytic leukemia (CLL) treated with one of two doses of rituximab combined with alemtuzumab to determine if the use of modified-dose rituximab significantly affects outcome.
Secondary
- To monitor and assess toxicity of these regimens.
- To determine the overall and progression-free survival, time to clinical response, time to next treatment, and duration of response in patients treated with these regimens
- To assess the correlation between risk stratification prognostic markers (i.e., CD38, ZAP-70, fluorescent in situ hybridization (FISH), and IgVH mutation) and clinical outcome.
- To assess response to these regimens using both the 1996 National Cancer Institute Working Group (NCI-WG 96) criteria and an expanded definition of response for patients in complete remission, including immunohistochemical examination of the bone marrow and sensitive flow cytometry (4-6 color) of blood for minimal residual disease and computed tomography (CT) scans for residual adenopathy.
- To determine the mechanism of action of rituximab and alemtuzumab and to determine mechanisms of resistance of a subpopulation of CLL cells to these drugs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of chronic lymphocytic leukemia (CLL) meeting the following criteria:
- •Minimum threshold peripheral lymphocyte count of 5 x 10^9/L (CLL variant) OR palpable adenopathy > 1 cm or palpable splenomegaly 9small lymphocytic lymphoma [SLL] variant)
- •Immunophenotypic demonstrations of a population of B-lymphocytes (as defined by CD19+) that are monoclonal (by light-chain exclusion) AND have ≥ 3 of the following characteristics:
- •Dim surface light chain expression
- •Dim surface CD20 expression
- •FISH analysis is negative for immunoglobulin heavy chain/cyclin D1 gene (IGH/CCND1) and/or immunostaining is negative for cyclin D1 expression (to exclude mantle cell lymphoma)
- •Progressive, symptomatic CLL, defined by at least one of the following:
- •Weight loss > 10% within the past 6 months attributable to progressive CLL (grade 2 or higher)
- •Extreme fatigue attributable to progressive CLL (grade 3 or higher)
- •Fevers > 100.5° F for 2 weeks without evidence of infection (grade 1 or higher)
- •Night sweats without evidence of infection (drenching)
- •Evidence of progressive bone marrow failure with hemoglobin < 11 g/dL or platelet count < 100 x 10^9/L
- •Rapidly progressive lymphadenopathy for which the largest node is ≤ 5 cm in any dimension
- •Largest lymph nodes involved in the neck, axilla, and groin need to be measured and followed for response
排除标准
- •Prior treatment for CLL
- •Massive splenomegaly > 6 cm below left costal margin, at rest, on clinical examination
- •Lymphadenopathy > 5 cm in any diameter
- •New York Heart Association class III or IV heart disease
- •Recent myocardial infarction (within the past month)
- •Uncontrolled infection
- •Infection with the human immunodeficiency virus (HIV/AIDS)
- •Serological evidence of active hepatitis B infection (HBsAg or HBeAg positive)
- •Positive hepatitis C serology
- •Evidence of active autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood cell aplasia
- •Other active primary malignancy requiring treatment or that limits survival to ≤ 2 years, except for in situ carcinoma of the cervix or breast or non-metastatic basal cell or squamous cell carcinoma of the skin
- •Major surgery within 4 weeks prior to pre-registration
- •Concomitant use of continuous systemic corticosteroids
- •Prior corticosteroids are allowed but not at time of pre-registration to the study
结局指标
主要结局
Proportion of Patients With Complete Response (CR)
时间窗: Assessed after 2 cycles of treatment and 2 months after completion of therapy
Response was evaluated using NCI-WG96 criteria. A CR requires all of the following for \>= 2 months: * Absence of lymphadenopathy \> 1 cm in diameter by physical examination * No hepatomegaly or splenomegaly on physical exam * No constitutional symptoms * Normal complete blood count (CBC) * Patients achieving a clinical CR with negative CT scan after 2 cycles of therapy are re-evaluated using immunohistochemical examination of bone marrow biopsy for residual CLL cells. Patients with no evidence of residual disease and no radiological evidence of residual CLL on CT scan of chest-abdomen-pelvis and no clinical evidence of CLL on clinical evaluation after completion of 2 cycles of therapy will be considered to have a CR with no evidence of residual disease
Proportion of Patients With Overall Response (OR)
时间窗: Assessed after 2 cycles of treatment and 2 months after completion of therapy
OR is defined as either CR, clinical CR, or partial response (PR) evaluated by NCI-WG96 criteria. CR has been defined in the other primary endpoint. A clinical CR requires all of the following: * Absence of lymphadenopathy by physical examination * No hepatomegaly or splenomegaly. Spleen and/or liver, if considered enlarged at baseline, should not be palpable, due to disease, on physical exam * Absence of constitutional symptoms * Normal CBC as exhibited by: A PR requires all the following for ≥2 months: * ≥50% decrease in peripheral blood lymphocyte count from baseline * ≥50% reduction in lymphadenopathy * ≥50% reduction in size of liver and/or spleen * Polymorphonuclear leukocytes ≥1.5x10\^9/L or 50% improvement over baseline * Platelets \>100x10\^9/L or 50% improvement over baseline * Hemoglobin \>11.0 gm/dl or 50% improvement over baseline without transfusions * Any constitutional symptoms
次要结局
- Progression-free Survival (PFS)(Assessed after 2 cycles of treatment, 2 months after completion of therapy and then yearly up to 5 years)
- Overall Survival (OS)(Assessed after 2 cycles of treatment, 2 months after completion of therapy and then yearly up to 5 years)
- Time to Response(Assessed after 2 cycles of treatment, 2 months after completion of therapy and then yearly up to 5 years)
- Duration of Response(Assessed after 2 cycles of treatment, 2 months after completion of therapy and then yearly up to 5 years)